Dermatophytosis, refers to the infection of the skin and nails, is a common public health concern worldwide. Very often, dermatophytosis is initiated by dermatophytic fungi. Tinea pedis, also known as athlete's foot, is the most common form of dermatophyte-causing skin disorder. In recent years, the incidence of tinea pedis has been increasing steadily, particularly in developed countries where as much as 15-25% of the population is affected [Fay Crawford]. This dermatophytic infection is often found in swimmers and runners whilst the infection rate was higher in their older age groups. The majority of athlete's foot cases are caused by Trichophyton rubrum and Trichophyton mentagrophytes. It is generally recognized that occlusion is the key to potentiate the dermatophytic infection of athlete's foot since shoes provide an enclosed environment with relatively high humidity and warmth that is ideal for the growth of the aforementioned dermatophytic fungi. The present invention significantly reduces the growth of Trichophyton rubrum and Trichophyton mentagrophytes when they are cultured with optimal environmental conditions.
The current mainstay fungicidal or fungistatic agents are majorly azoles, which can be further categorized into itraconazole, ketoconazole and fluconazole. Among them, fluconazole is considered to exert the greatest minimum inhibitory concentration (MIC) against a wide spectrum of fungi. However, Trichophyton rubrum and Trichophyton mentagrophytes showed notable resistance to the three aforementioned azoles at varies levels. Therefore, the discovery and development of new and potent anti-fungal agents are highly demanded.
Over the past decades, a number of pharmacological studies have been focused on the use of drug-like small molecules as therapeutic agents derived from herbal constituents, particularly polyphenolic stilbenoids. In fact, stilbenoids are a category of compounds composed of a general C6-C2-C6 structure, and they are often isolated as monomers and oligomers for their applications as botanical supplements or active constituents in medicinal preparations. As suggested by a growing body of evidence that stilbenoids are potent antioxidants since most of them are produced as phytoalexins against abiotic and biotic stress factors. In addition, some of the stilbenoids have been reported with anti-microbial activity, particularly against fungal growth.
Therefore, using dihydro-resveratrol or its dihydrostilbene derivatives and/or chemical variants to formulate an anti-fungal agent becomes one of the objectives of the present invention.
Apart from dermatophytosis, dental caries (cariogenesis) is also a common public health concern worldwide. In general, cariogenesis is characterized by the cessation or erosion of the hard tissues of the teeth, which can result in dental pain, sensitive teeth and loss of viability of the teeth. Food containing fermentable carbohydrates, majorly mono-, di-, and polysaccharides, have long been recognized as a major contributing cause of dental caries because they serve as an easily utilizable source of nutrition for bacteria, such as Streptococcus mutans and Streptococcus sobrinus, found in the oral cavity [van Houte J]. In fact, these gram-positive bacteria are aciduric (acid-tolerant) and acidogenic (acid-producing); they metabolize the dietary sugars, explicitly sucrose, to lactic acid, which causes demineralization of enamel and dentin. Meanwhile, their synthesis of sticky macromolecules, such as polysaccharides, fosters the attachment of bacteria to the surface of the teeth by the formation of dental plaques and biofilms. As a result, dental caries develops. Furthermore, these aciduric and acidogenic streptococci are essentially recovered on cultivation of initial and established carious lesions. Inhibition of the aforementioned streptococci, Streptococcus mutans in particular, would be obviously beneficial to the decrease of dental plaques and biofilms, so as the occurrence of dental caries. The present invention significantly reduces the growth of Streptococcus mutans and Streptococcus sobrinus when they are cultured with optimal environmental conditions.
Therefore, methods of using dihydro-resveratrol or its dihydrostilbene derivatives and/or chemical variants as an anti-bacterial agent in a subject become another objective of the present invention.